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First published online on February 13, 2004.
 Copyright © 2004 by The Physiological Society
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jphysiol.2003.058230v1
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Received November 17, 2003
Revised December 23, 2003
Accepted after revision February 13, 2004

Activation of GABAA receptors containing the {alpha}4 subunit by GABA and pentobarbital

Gustav Akk1*, John Bracamontes1, and Joe Henry Steinbach2

1 Washington University in St Louis
2 Washington University

* To whom correspondence should be addressed. E-mail: akk{at}morpheus.wustl.edu.

The activation properties of GABAA receptors containing {alpha}4{beta}2{gamma}2 and {alpha}4{beta}2{delta} subunits were examined in the presence of GABA or pentobarbital. The receptors were expressed transiently in HEK 293 cells, and the electrophysiological experiments were carried out using cell-attached single-channel patch clamp or whole-cell macroscopic recordings. The data show that GABA is a stronger activator of {alpha}4{beta}2{gamma}2 receptors than {alpha}4{beta}2{delta} receptors. Single-channel clusters were recorded from {alpha}4{beta}2{gamma}2 receptors in the presence of 10-5000 µM GABA. The maximal intracluster open probability was 0.35 with a half-maximal response elicited by 32 µM GABA. Simultaneous kinetic analysis of single-channel currents obtained at various GABA concentrations yields a channel opening rate constant of 250 s-1, and a KD of 20 µM. In contrast, only isolated openings were observed in the presence of GABA for the {alpha}4{beta}2{delta} receptor. Pentobarbital was a strong activator of both {alpha}4{beta}2{gamma}2 and {alpha}4{beta}2{delta} receptors. The maximal cluster open probability, recorded in the presence of 100 µM pentobarbital, was 0.7. At higher pentobarbital concentrations, the cluster open probability was reduced, likely due to channel block. The results from single-channel experiments were confirmed by macroscopic recordings from HEK cells in the presence of GABA or pentobarbital.


Key words: Channel gating • GABA receptor • Pentobarbital




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